PURPOSE: To measure parameters of the cardiac cycle-induced pulsatile light absorption signal (plethysmography signal) of the optic nerve head (ONH) and to compare parameters between normal subjects and patients with different stages of glaucoma. PATIENTS AND METHODS: A recently developed video ophthalmoscope was used to acquire short video sequences (10 s) of the ONH. After image registration and trend correction, the pulsatile changing light absorption at the ONH tissue (excluding large vessels) was calculated. The changing light absorption depends on the pulsatile changing blood volume. Various parameters, including peak amplitude, steepness, time-to-peak, full width at half maximum (FWHM), and pulse duration, were calculated for averaged individual pulses (heartbeats) of the plethysmography signal. This method was applied to 19 healthy control subjects and 91 subjects with ocular hypertension, as well as different stages of primary open-angle glaucoma (17 subjects with ocular hypertension, 24 with preperimetric glaucoma, and 50 with perimetric glaucoma). RESULTS: Compared to the normal subjects, significant reductions (p < 0.001) in peak amplitude and steepness were observed in the group of perimetric glaucoma patients, but no significant difference was found for time-to-peak, FWHM, and pulse duration. Peak amplitude and steepness showed high correlations with RNFL thickness (p < 0.001). CONCLUSIONS: The presented low-cost video-ophthalmoscope permits measurement of the plethysmographic signal of the ONH tissue and calculation of different blood flow-related parameters. The reduced values of the amplitude and steepness parameters in perimetric glaucoma patients suggest decreased ONH perfusion and blood volume. This outcome is in agreement with results from other studies using OCT angiography and laser speckle flowgraphy, which confirm reduced capillary density in these patients. Registration site: www.clinicaltrials.gov , Trial registration number: NCT00494923.

Department of Biomedical Engineering Faculty of Electrical Engineering and Communication Brno University of Technology 616 00 Brno Czech Republic

Department of Ophthalmology Friedrich Alexander University of Erlangen Nuremberg 91054 Erlangen Germany

Zobrazit více v PubMed

Flammer J, Orgül S, Costa VP, et al. The impact of ocular blood flow in glaucoma. Prog Retin Eye Res. 2002;21:359–393. doi: 10.1016/S1350-9462(02)00008-3. PubMed DOI

Schubert G. Untersuchung des Blutsauerstoffgehaltes und der Durchblutung des Auges auf lichtelektrischem Wege. Albrecht Von Graefes Arch Ophthalmol. 1936;135:558–560. doi: 10.1007/BF01853424. DOI

Trokel S. Measurement of ocular blood flow and volume by reflective densitometry. Arch Ophthalmol. 1964;71:88–92. doi: 10.1001/archopht.1964.00970010104017. PubMed DOI

Trokel S. Photometric study of ocular blood flow in man. Arch Ophthalmol. 1964;71:528–530. doi: 10.1001/archopht.1964.00970010544018. PubMed DOI

Beintema DK, Mook GA, Worst JGF. Recording of arm-to-retina circulation-time by means of fundus reflectometry. Ophthalmologica. 1964;148:163–168. doi: 10.1159/000304680. PubMed DOI

Matsuo H, Kogure F, Takahasi K (1966) Studies of the photoelectric plethysmogram of the eye. Procceedings XX Int Congr Ophthalmol 1966 178–182

Tornow RP, Kopp O, Schultheiss B (2003) Time course of fundus reflection changes according to the cardiac cycle. In: Invest. Ophthalmol. Vis. Sci. pp 1296-ARVO Abstract

Tornow RP, Kopp O (2006) Time course and frequency spectrum (0 to 12,5 Hz) of fundus reflection. In: Invest. Ophthalmol. Vis. Sci. pp 3753-ARVO Abstract

Lovasik JV, Gagnon M, Kergoat H. A novel noninvasive videographic method for quantifying changes in the chromaticity of the optic nerve head with changes in the intraocular pressure, pulsatile choroidal blood flow and visual neural function in humans. Surv Ophthalmol. 1994;38(Suppl):S35–S51. doi: 10.1016/0039-6257(94)90045-0. PubMed DOI

Morgan WH, Hazelton ML, Betz-Stablein BD, et al. Photoplethysmographic measurement of various retinal vascular pulsation parameters and measurement of the venous phase delay. Investig Ophthalmol Vis Sci. 2014;55:5998–6006. doi: 10.1167/iovs.14-15104. PubMed DOI

Hassan H, Jaidka S, Dwyer VM, Hu S. Assessing blood vessel perfusion and vital signs through retinal imaging photoplethysmography. Biomed Opt Express. 2018;9:2351. doi: 10.1364/boe.9.002351. PubMed DOI PMC

Briers JD. Laser Doppler and time-varying speckle: a reconciliation. J Opt Soc Am A. 1996;13:345. doi: 10.1364/josaa.13.000345. DOI

Briers JD. Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging. Physiol Meas. 2001;22:R35–R66. doi: 10.1088/0967-3334/22/4/201. PubMed DOI

Michelson G, Schmauss B. Two dimensional mapping of the perfusion of the retina and optic nerve head. Br J Ophthalmol. 1995;79:1126–1132. doi: 10.1136/bjo.79.12.1126. PubMed DOI PMC

Wang RK, Jacques SL, Ma Z, et al. Three dimensional optical angiography. Opt Express. 2007;15:4083. doi: 10.1364/oe.15.004083. PubMed DOI

Jia Y, Morrison JC, Tokayer J, et al. Quantitative OCT angiography of optic nerve head blood flow. Biomed Opt Express. 2012;3:3127. doi: 10.1364/boe.3.003127. PubMed DOI PMC

Zhang A, Zhang Q, Chen C-L, Wang RK. Methods and algorithms for optical coherence tomography-based angiography: a review and comparison. J Biomed Opt. 2015;20:100901. doi: 10.1117/1.jbo.20.10.100901. PubMed DOI PMC

Gao SS, Jia Y, Zhang M, et al. Optical coherence tomography angiography. Investig Ophthalmol Vis Sci. 2016;57:OCT27–OCT36. doi: 10.1167/iovs.15-19043. PubMed DOI PMC

Hagag AM, Gao SS, Jia Y, Huang D. Optical coherence tomography angiography: technical principles and clinical applications in ophthalmology. Taiwan J Ophthalmol. 2017;7:115–129. doi: 10.4103/tjo.tjo_31_17. PubMed DOI PMC

Gräfe MGO, Gondre M, de Boer JF. Precision analysis and optimization in phase decorrelation OCT velocimetry. Biomed Opt Express. 2019;10:1297. doi: 10.1364/boe.10.001297. PubMed DOI PMC

Chen C-L, Bojikian KD, Gupta D, et al. Optic nerve head perfusion in normal eyes and eyes with glaucoma using optical coherence tomography-based microangiography. Quant Imaging Med Surg. 2016;6:125. doi: 10.21037/QIMS.2016.03.05. PubMed DOI PMC

Wang X, Jiang C, Ko T, et al. Correlation between optic disc perfusion and glaucomatous severity in patients with open-angle glaucoma: an optical coherence tomography angiography study. Graefes Arch Clin Exp Ophthalmol. 2015;253:1557–1564. doi: 10.1007/s00417-015-3095-y. PubMed DOI

Rao HL, Kadambi SV, Weinreb RN et al (2017) Diagnostic ability of peripapillary vessel density measurements of optical coherence tomography angiography in primary open-angle and angle-closure glaucoma. Br J Ophthalmol 101. 10.1136/bjophthalmol-2016-309377 PubMed

Chihara E, Dimitrova G, Amano H, Chihara T. Discriminatory power of superficial vessel density and prelaminar vascular flow index in eyes with glaucoma and ocular hypertension and normal eyes. Investig Ophthalmol Vis Sci. 2017;58:690–697. doi: 10.1167/iovs.16-20709. PubMed DOI

Lommatzsch C, Rothaus K, Koch JM, et al. Vessel density in OCT angiography permits differentiation between normal and glaucomatous optic nerve heads. Int J Ophthalmol. 2018;11:835–843. doi: 10.18240/ijo.2018.05.20. PubMed DOI PMC

Konishi N, Tokimoto Y, Kohra K, Fujii H (2002) New laser speckle flowgraphy system using CCD camera. Opt Rev. 10.1007/s10043-002-0163-4

Luft N, Wozniak PA, Aschinger GC, et al. Ocular blood flow measurements in healthy white subjects using laser speckle flowgraphy. PLoS One. 2016;11:e0168190. doi: 10.1371/journal.pone.0168190. PubMed DOI PMC

Mursch-Edlmayr AS, Luft N, Podkowinski D, et al. Laser speckle flowgraphy derived characteristics of optic nerve head perfusion in normal tension glaucoma and healthy individuals: a Pilot study. Sci Rep. 2018;8:5343. doi: 10.1038/s41598-018-23149-0. PubMed DOI PMC

Yokoyama Y, Aizawa N, Chiba N, et al. Significant correlations between optic nerve head microcirculation and visual field defects and nerve fiber layer loss in glaucoma patients with myopic glaucomatous disk. Clin Ophthalmol. 2011;5:1721–1727. doi: 10.2147/OPTH.S23204. PubMed DOI PMC

Shiga Y, Kunikata H, Aizawa N, et al. Optic nerve head blood flow, as measured by laser speckle flowgraphy, is significantly reduced in preperimetric glaucoma. Curr Eye Res. 2016;41:1447–1453. doi: 10.3109/02713683.2015.1127974. PubMed DOI

Shiga Y, Omodaka K, Kunikata H, et al. Waveform analysis of ocular blood flow and the early detection of normal tension glaucoma. Investig Ophthalmol Vis Sci. 2013;54:7699–7706. doi: 10.1167/iovs.13-12930. PubMed DOI

Tornow R-P, Odstrcilik J, Kolar R. Time-resolved quantitative inter-eye comparison of cardiac cycle-induced blood volume changes in the human retina. Biomed Opt Express. 2018;9:6237. doi: 10.1364/boe.9.006237. PubMed DOI PMC

Tornow RP, Kolar R, Odstrcilik J (2015) Non-mydriatic video ophthalmoscope to measure fast temporal changes of the human retina. In: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. p 954006

Jonas JB, Gusek GC, Naumann GOH (1988) Optic disc morphometry in chronic primary open-angle glaucoma - I. Morphometric intrapapillary characteristics. Graefes Arch Clin Exp Ophthalmol. 10.1007/BF02169199 PubMed

Jonas JB, Budde WM, Panda-Jonas S (1999) Ophthalmoscopic evaluation of the optic nerve head. Surv Ophthalmol. 10.1016/S0039-6257(98)00049-6 PubMed

Skuta GL. Automated static perimetry. Am J Ophthalmol. 1992;114:110–111. doi: 10.1016/s0002-9394(14)77431-8. DOI

Bendschneider D, Tornow RP, Horn FK et al (2010) Retinal nerve fiber layer thickness in normals measured by spectral domain oct. J Glaucoma 19. 10.1097/IJG.0b013e3181c4b0c7 PubMed

Kolar R, Tornow RP, Odstrcilik J, Liberdova I. Registration of retinal sequences from new video-ophthalmoscopic camera. Biomed Eng Online. 2016;15:57. doi: 10.1186/s12938-016-0191-0. PubMed DOI PMC

Odstrcilik J, Kolar R, Harabis V, Tornow RP (2015) Classification-based blood vessel segmentation in retinal images. In: Computational Vision and Medical Image Processing V. CRC Press, pp 95–100

Lévêque P-MM, Zéboulon P, Brasnu E, et al. Optic disc vascularization in glaucoma: value of spectral-domain optical coherence tomography angiography. J Ophthalmol. 2016;2016:1–9. doi: 10.1155/2016/6956717. PubMed DOI PMC

Van Melkebeke L, Barbosa-Breda J, Huygens M, Stalmans I (2018) Optical coherence tomography angiography in glaucoma: a review. Ophthalmic Res. 10.1159/000488495 PubMed

Takeyama A, Ishida K, Anraku A, et al. Comparison of optical coherence tomography angiography and laser speckle flowgraphy for the diagnosis of normal-tension glaucoma. J Ophthalmol. 2018;2018:1–9. doi: 10.1155/2018/1751857. PubMed DOI PMC

Lawrence C, Schlegel WA. Ophthalmic pulse studies. I. Influence of intraocular pressure. Investig Ophthalmol. 1966;5:515–525. PubMed

Michelson G, Patzelt A, Harazny J (2002) Flickering light increases retinal blood flow. In: Retina, 2002/06/11. pp 336–343 PubMed

Crittin M, Riva CE. Functional imaging of the human papilla and peripapillary region based on flicker-induced reflectance changes. Neurosci Lett. 2004;360:141–144. doi: 10.1016/j.neulet.2004.02.063. PubMed DOI

Best M, Plechaty G, Harris L, Galin MA. Ophthalmodynamometry and ocular pulse studies in carotid occlusion. Arch Ophthalmol. 1971;85:334–338. doi: 10.1001/archopht.1971.00990050336019. PubMed DOI

Perkins ES. The ocular pulse and intraocular pressure as a screening test for carotid artery stenosis. Br J Ophthalmol. 1985;69:676–680. doi: 10.1136/bjo.69.9.676. PubMed DOI PMC

Kinsner W, Yan Y. A model of the carotid vascular system with stenosis at the carotid bifurcation. Math Comput Model. 1990;14:582–585. doi: 10.1016/0895-7177(90)90249-M. DOI

Rina M, Shiba T, Takahashi M et al (2015) Pulse waveform analysis of optic nerve head circulation for predicting carotid atherosclerotic changes. Graefes Arch Clin Exp Ophthalmol. 10.1007/s00417-015-3123-y PubMed

Knecht PB, Menghini M, Bachmann LM, et al. The ocular pulse amplitude as a noninvasive parameter for carotid artery stenosis screening: a test accuracy study. Ophthalmology. 2012;119:1244–1249. doi: 10.1016/j.ophtha.2011.12.040. PubMed DOI

Pinto LA, Vandewalle E, de Clerck E, et al. Ophthalmic artery Doppler waveform changes associated with increased damage in glaucoma patients. Investig Ophthalmol Vis Sci. 2012;53:2448–2453. doi: 10.1167/iovs.11-9388. PubMed DOI

Millasseau SC, Guigui FG, Kelly RP, et al. Noninvasive assessment of the digital volume pulse. Comparison with the peripheral pressure pulse. Hypertens (Dallas, Tex 1979) 2000;36:952–956. doi: 10.1161/01.hyp.36.6.952. PubMed DOI

Levine RA, Demirel S, Fan J, et al. Asymmetries and visual field summaries as predictors of glaucoma in the ocular hypertension treatment study. Invest Ophthalmol Vis Sci. 2006;47:3896–3903. doi: 10.1167/iovs.05-0469. PubMed DOI PMC

Sullivan-Mee M, Ruegg CC, Pensyl D, et al. Diagnostic precision of retinal nerve fiber layer and macular thickness asymmetry parameters for identifying early primary open-angle glaucoma. Am J Ophthalmol. 2013;156:567–577.e1. doi: 10.1016/j.ajo.2013.04.037. PubMed DOI

Hou H, Moghimi S, Zangwill LM, et al. Inter-eye asymmetry of optical coherence tomography angiography vessel density in bilateral glaucoma, glaucoma suspect, and healthy eyes. Am J Ophthalmol. 2018;190:69–77. doi: 10.1016/j.ajo.2018.03.026. PubMed DOI PMC

Comparative analysis of retinal photoplethysmographic spatial maps and thickness of retinal nerve fiber layer

A multi-color video-ophthalmoscopes allows to measure the spectral distribution of light absorption of blood in the human retina

Heart rate and age modulate retinal pulsatile patterns

Photoplethysmographic analysis of retinal videodata based on the Fourier domain approach

Zobrazit více v PubMed

ClinicalTrials.gov
NCT00494923